Identification and characterization of a non-conventional CD45 negative perivascular macrophage population within the mouse brain.

Abstract Perivascular macrophages (pvM) are closely associated with cerebral vasculature and play an essential role in drainage of the brain and regulation of the immune response. Here, using reporter mouse models and immunofluorescence on sections and whole brain, flow cytometry and single cell sequencing, we identify a Lyve1+ brain perivascular population lacking classical macrophage markers such as CD45 and Cx3cr1. We named the new non-conventional CD45 negative perivascular macrophages pvM2. These cells have a similar location, morphology and phagocytic function as conventional pvM. The pvM2 are not derived from hematopoietic stem cells, as they are negative in the VavtdT lineage tracing model. They increase in number after photothrombotic induced stroke established by flow cytometry and 3D immunofluorescence analysis. Since CD45 negative cells were typically excluded from macrophage studies, the presence of pvM2 has been previously missed and their role is of importance to assess in the brain disease models.